Dose Escalation in Esophageal Cancer: Comparing Pre-Accrual and On-Trial Target Volume Delineation in the UK SCOPE2 Trial

Abstract

The ongoing UK SCOPE2 trial evaluates radiotherapy (RT) dose escalation and PET-guided systemic therapy in esophageal cancer, and has an accompanying RT trials quality assurance (RTTQA) program, evolved through the preceding SCOPE trials. We compare pre-accrual with on-trial individual case review (ICR) target volume delineation (TVD). Prior to recruitment, centers were required to undertake TVD exercises using 3D/4D DICOM datasets with relevant clinical details and a RT planning guidance document (RPGD) provided. Contours were then compared against the RTTQA team-defined gold standard. Exceptions were those who had satisfied QA requirements for a previous esophageal RT trial (NeoSCOPE). For ICRs, prospective reviews (prior RT start, PRs) were undertaken for each center's first submission, plus high-dose cases submitted pending formal safety review. Additional PRs were undertaken at the RTTQA team's discretion. Timely retrospective reviews (within 2 weeks of RT start, TRR) were also undertaken for a random 10% sample. TVDs were assessed for compliance using predefined criteria and the RPGD. Resubmission was requested at reviewer's discretion, usually due to unacceptable variation (UV) from protocol. Clarification was sought before contour approval/resubmission request if appropriate. Review outcomes were then evaluated. PTV6000 was new to SCOPE2, along with a greater emphasis on use of 4DCT than in prior SCOPE trials. A total of 85 pre-accrual cases from 33 UK centers were reviewed, of which 20 (24%) were resubmissions, and 50 (59%) were accepted. 99 TVD UVs were observed in 49 cases, most commonly in CTVB (42/99, 42%), which included editing for normal structures and elective lymph node regions, followed by ITV (4D cases only, 14/52, 27%) and PTV6000 (13/99, 13%). 121 ICRs from 31 UK centers were available for review. 87 (72%) were PRs and 34 (28%) TRRs. 43 (36%) completed the relevant SCOPE2 exercise. 19 (16%) were resubmissions, and 82 (68%) were accepted. 72 UVs were observed in 45 ICRs; again, most commonly in CTVB (34/72, 48%), PTV6000 (high dose arm only, 11/46, 24%) and ITV (4D only, 5/26, 19%). Of the 45 cases where a UV was recorded, 16 (36%) had completed the relevant SCOPE2 pre-accrual. Comparing area of UV on SCOPE2 pre-accrual cases and ICRs, 3 (19%) contours contained the same (2 = CTVB, 1 = PTV6000), 5 (31%) contained different and 8 (50%) had no UVs at pre-accrual. The rate of UV was significantly lower for ICR than for pre-accrual submissions (0.60 and 1.16 respectively, p = 0.001). Significantly fewer UVs in ICR compared with pre-accrual supports a robust, educational RTTQA program through national collaboration and evolving trial series. CTVB, along with newer volumes of ITV and PTV6000, were recurring UV domains and should inform RPGD development and RTTQA for ongoing recruitment and future trials.